Ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate → (R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

HRID 877744Notes

Reaction equation

HRID 877744 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:12]=[C:6]2[C:5]=1Cl)(=[O:3])[NH2:2].[NH2:19][C@@H:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][C:21]1([CH3:34])[CH3:33]>>[C:29]([O:28][C:26]([N:23]1[CH2:24][CH2:25][C@@H:20]([NH:19][C:5]2[C:6]3[N:7]([CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:12]=3)[N:8]=[CH:9][C:4]=2[C:1](=[O:3])[NH2:2])[C:21]([CH3:34])([CH3:33])[CH2:22]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

3

Reactant 2

HCID 68290691Ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate2×HCID 68945318(R)-Tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate2×

Product 1

HCID 68350368(R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylateYield 99%

Procedure

Following the conditions described in Step 2 of Example 1, ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (Intermediate 1, 0.7 g, 2.62 mmol,) was reacted with (R)-tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate (Intermediate 6, 0.657 g, 2.88 mmol) to give (R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (1.187 g, 99% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 8.05 (d, J=1.8 Hz, 1H), 7.92 (s, 1H), 7.22 (d, J=1.5 Hz, 1H), 5.44 (br. s., 2H), 4.38 (q, J=7.1 Hz, 2H), 4.14-3.93 (m, J=9.6, 9.6, 3.7 Hz, 2H), 3.73 (br. s., 1H), 3.14 (br. s., 1H), 2.89 (br. s., 1H), 2.09-2.00 (m, 1H), 1.84-1.72 (m, 1H), 1.49 (s, 9H), 1.40 (t, J=7.2 Hz, 3H), 1.11 (s, 3H), 1.03 (s, 3H); MS (ES+) m/z: 460.3 (M+H); LC retention time: 4.250 min (analytical HPLC Method H).

Sources & evidence

ORD record
ord-32132cdc1da14e4fab792caace170b70
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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